In the pharmaceutical, biotechnology and even food, beverage and cosmetics industries, it is often desired to provide a processing system that is capable of handling fluids in a sterile manner. This is designed to prevent unwanted, often dangerous organisms, such as bacteria as well as environmental contaminants, such as dust, dirt and the like from entering into the process stream and/or end product. It would be desirable to have a completely sealed system but this is not always possible with the processes that take place in production.
There is a need for the introduction or removal of materials from the process stream in order to add components of the product, such as media or buffers to a bioreactor; withdraw samples from the process stream to check for microbial contamination, quality control, process control, etc; and to fill the product into its final container such as vials, syringes, sealed boxes, bottles and the like.
Typically, the systems have been made of stainless steel and the system is exposed to live steam before use and then cleaned with chemicals such as caustic solutions after use to ensure that all contaminants are removed.
Steaming is the most effective means of sterilization. The use of steam in a set system is known as steaming in place or SIP. Saturated steam carries 200 times the BTU heat transfer capacity of heated air because of the latent heat released by the steam as it changes from vapor to liquid.
Several disadvantages exist with the use of steam. Any connections to or openings of the system made after the system has been SIP'd is an aseptic (but not sterile) connection or opening. This increases the risk of contamination of the entire system. One typically uses alcohol wipes or an open flame to clean the components to be connected, (e.g. connecting a sample collection bag to a system after SIP has occurred) and thus minimize the risk of contamination.
Also the high temperatures and pressure differentials of the steam make the selection of materials and components very difficult and limited and even then an accidental pressure differential at high temperatures can cause a non-steel component to fail.
Additionally, such systems that are reused need to undergo rigorous testing and validation to prove to the necessary authorities that the system is sterile before each use. The expense of validation as well as the cleaning regiment required is very high and very time consuming (typically taking 1 to 2 years for approval). In addition, some components are very difficult to adequately clean after use.
As an alternative to requiring a sterilization step with steam, some systems have advocated the use of alcohol wipes and other bactericides on the adjoining parts before assembly. While this may significantly reduce the presence of organisms, it does not eliminate them and at best this provides an aseptic connection.
U.S. Pat. No. 6,341,802 teaches the use of peelable membranes formed on the outer surfaces of two mating components. The membranes are exposed to the environment. Layers beneath of two outer membranes are sterile. The membranes are mated and the two devices attached and the membranes are then pulled out of the union between the two components. A piercable probe extends through the sterile barriers that face each other to form an environmentally tight seal. This approach is cumbersome and there is still some risk of contamination in the removal of the outer membranes. Also the use of piercing device creates the generation of particles that are unacceptable as well as the potential for tearing the seals between the two components that might add more contaminants to the system or clog the openings. Lastly, the device is limited in size making its use at large volumes or flows impracticable.
In a further improvement, a connector or valve can be formed that has a nonsterile closed face and a presterilized (typically with gamma radiation) downstream component(s) (such as a tubing and bag assembly). The face of the device is then attached to the desired equipment such as a port of a bioreactor or storage tank, or attached to a pipe fitting by a Tri-Clover® or Ladish fitting. The face along with the rest of the system upstream of the face is then steam sterilized in place (SIP). When the face is open after steaming, a sterile connection is achieved.
What is still desired is a simple, reliable sterile connection device that allows for a sterile to sterile connection without the need for steam or other cumbersome procedures.